Altered methylation and expression patterns of genes regulating placental nitric oxide pathway in patients with severe preeclampsia.

Abstract

Pre-eclampsia is a common pregnancy disorder syndrome whose molecular mechanism is not clear. Nitric oxide (NO) is a key regulator of placentation. Reduction of NO has previously been associated with endothelial dysfunction in pre-eclamptic women. Therefore, we measured expression and methylation of some placental genes that were involved in NO pathway like named ARG II, PRMT1 and DDAH2 in pre-eclampsia and normal pregnancies in order to determine whether impairment of expression of these genes in the pre-eclamptic placenta could contribute to development of disease. ARG II, PRMT1 expressions as well as DDAH2 expression and methylation, in placentas collected from 59 patients with preeclampsia and 40 normotensive pregnancies were measured using real-time PCR and methylation specific PCR, respectively. The relationship among ARG II, PRMT1 and DDAH2 expressions was analyzed statistically. ARG II expression was increased, PRMT1 expression was not significantly changed. DDAH2 expression was decreased and qualitative methylation patterns were 32/59 and 21/40 in placentas from patients with pre-eclampsia compared with control group, respectively. The alterations in ARG II and DDAH2 expressions in pre-eclampsia patients maybe correlated with decreased eNOS expression. These findings indicate that ARG II and DDAH2 may be involved in pre-eclampsia pathogenesis and could be potential therapeutic targets for this disease.